1. Field of the Invention
This invention relates to novel 4-anilinofuro[2,3-b]quinoline derivatives, which exhibit a broad and potent anticancer activity and improved solubility in water and oral bioavailability. This invention also relates to processes for preparing these derivatives, as well as the uses of the same in the manufacture of pharmaceutical compositions and in the treatment of cancers.
2. Description of the Related Art
Acridine derivatives are compounds having an acridine moiety, which is a planar tricyclic structure. The acridine derivatives are able to inhibit topoisomerase II by intercalating the acridine moiety thereof into DNA, thereby being capable of blocking DNA replication and transcription. Accordingly, the acridine derivatives, especially 9-anilinoacridine derivatives, have been extensively studied as potential chemotherapeutic agents (Denny W. A. et al. (1987), J. Med. Chem., 30:658-663; Gamage S. A. et al. (1994), J. Med. Chem., 37:1486-1494; and Gamage S. A. et al. (1997), J. Med. Chem., 40:2634-2642).
In order to develop a new potent anticancer drug, the applicants synthesized a series of 4-anilinofuro[2,3-b]quinoline derivatives by replacing a benzene ring of the acridine moiety of 9-anilinoacridine with a furan ring (U.S. Pat. No. 6,750,223 B2; Chen I. L. et al. (2002), Helv. Chem. Acta., 85:2214-2221; Zhao Y. L. et al. (2005), Chem. Biodiver., 2:205-214: Chen Y. L. et al. (2005), J. Med. Chem., 40:928-934; and Chen Y. L. et al., (2008), Chem. Biodiver., 4:267-278). The thus obtained 4-anilinofuro[2,3-b]quinoline derivatives are structurally related to the 9-anilinoacridine derivatives.
Among the aforesaid 4-anilinofuro[2,3-b]quinoline derivatives synthesized by the applicants, 1-(4-(furo[2,3-b]quinolin-4-ylamino)phenyl)ethanone (referred to as compound 1 hereinafter) was verified to have an antiproliferative potency higher than that of amsacrine (m-AMSA), which is a 9-anilinoacridine derivative clinically used for treatment of leukemia and lymphoma, in an in vitro anticancer assay.
